The Molecular Pathology and Immunology Core of the University of Florida currently assists multiple investigators participating in Projects aimed at an improved understanding of the pathogenesis of type 1 diabetes, as well as the development of agents capable of reversing and/or preventing the disease. Specifically, the Core supports these investigations by performing pathological and immunological analyses that characterize the host's immune system and cell/tissue response, including those involving treatments proposed or currently used in experimental and preclinical studies. This goal has and will continue to be accomplished by performance of three specific aims: 1) Determine tissue morphology in the context of histopathology in order to evaluate treatment effects with respect to administration site, dose, and treatment duration. 2) Determine the potential beneficial effects of treatments in murine models of diabetes;with assessment of the pancreas as well other organs related to type 1 diabetes. 3) Perform immunologic evaluations in animal models and human subjects that characterize aspects related to the humoral and cellular immune response, as well as providing genetic susceptibility to type 1 diabetes. The morphological studies are vital in order to evaluate whether a given Project's intervention successfully ameliorates the pro- inflammatory environment within the pancreas, lymph node, spleen, and other organs and to determine the extent to which any intervention induces acute inflammation or cytotoxicity. Centralization of the morphological studies, and standardization of the histopathological and toxicological determinants, enables rigorous assessment of cellular responses. Procedures include standard histology on paraffin and frozen materials, special stains, histochemistry, immunohistochemistry, and immunofluorescence. In terms of analysis of human samples, the Core laboratory will build upon more that two decades of experience in terms of evaluating for the presence of autoantibodies in serum of patients with or at increased-risk of type 1 diabetes, as well as determining the genetic susceptibility for the disease by performance of HLA typing. In addition to providing a critical element for assurance of therapeutic safety and improved mechanistic understanding, the Core should provide information that will enhance the feasibility and efficacy of preclinical trials to prevent or reverse type 1 diabetes.